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The first historical account of muscular dystrophy appeared in 1830, when Sir Charles Bell wrote an essay about an illness that caused progressive weakness in boys. Six years later, another scientist reported on two brothers who developed generalized weakness, muscle damage, and replacement of damaged muscle tissue with fat and connective tissue. At that time the symptoms were thought to be signs of tuberculosis.[How to reference and link to summary or text]

In the 1850s, descriptions of boys who grew progressively weaker, lost the ability to walk, and died at an early age became more prominent in medical journals. In the following decade, French neurologist Guillaume Duchenne gave a comprehensive account of 13 boys with the most common and severe form of the disease (which now carries his name — Duchenne muscular dystrophy). It soon became evident that the disease had more than one form, and that these diseases affected people of either sex and of all ages. [How to reference and link to summary or text]

These conditions are inherited, and the different muscular dystrophies follow various inheritance patterns
The best-known type, Duchenne muscular dystrophy (DMD), is inherited in an X-linked recessive pattern, meaning that the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes, and is thus considered sex-linked. In males (who have only one X chromosome) one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes) a mutation must generally be present in both copies of the gene to cause the disorder (relatively rare exceptions, manifesting carriers, do occur due to dosage compensation/X-inactivation). Males are therefore affected by X-linked recessive disorders much more often than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
In about two thirds of DMD cases, an affected male inherits the mutation from a mother who carries one altered copy of the DMD gene. The other one third of cases probably result from new mutations in the gene. Females who carry one copy of a DMDmutation may have some signs and symptoms related to the condition (such as muscle weakness and cramping), but these are typically milder than the signs and symptoms seen in affected males.
Duchenne muscular dystrophy and Becker's muscular dystrophy are caused by mutations of the gene for the dystrophinprotein and lead to an overabundance of the enzymecreatine kinase.[5][6] The dystrophin gene is the largest gene in humans.[7]

When muscle cells undergo injury, quiescent satellite cells are released from beneath the basement membrane. They become activated and re-enter the cell cycle. These dividing cells are known as the "transit amplifying pool" before undergoing myogenic differentiation to form new (post-mitotic) myotubes. There is also evidence suggesting that these cells are capable of fusing with existing myofibers to facilitate growth and repair.

The process of muscle regeneration involves considerable remodeling of extracellular matrix and, where extensive damage occurs, is incomplete. Fibroblasts within the muscle deposit scar tissue, which can impair muscle function, and is a significant part of the pathology of muscular dystrophies.

Satellite cells proliferate following muscle trauma (Seale, et al., 2003) and form new myofibers through a process similar to foetal muscle development (Parker, et al., 2003). After several cell divisions, the satellite cells begin to fuse with the damaged myotubes and undergo further differentiations and maturation, with peripheral nuclei as in hallmark (Parker, et al., 2003). One of the first roles described for IGF-1 was its involvement in the proliferation and differentiation of satellite cells. In addition, IGF-1 expression in skeletal muscle extends the capacity to activate satellite cell proliferation (Charkravarthy, et al., 2000), increasing and prolonging the beneficial effects to the aging muscle.

The diagnosis of muscular dystrophy is based on the results of a muscle biopsy. In some cases, a DNA blood test may be all that is needed.

A physical examination and the patient's medical history will help the doctor determine the type of muscular dystrophy. Specific muscle groups are affected by different types of muscular dystrophy.

Often, there is a loss of muscle mass (wasting), which may be hard to see because some types of muscular dystrophy cause a build up of fat and connective tissue that makes the muscle appear larger. This is called pseudohypertrophy.

The prognosis for people with muscular dystrophy varies according to the type and progression of the disorder. Some cases may be mild and progress very slowly over a normal lifespan, while others produce severe muscle weakness, functional disability, and loss of the ability to walk. Some children with muscular dystrophy die in infancy while others live into adulthood with only moderate disability. The muscles affected vary, but can be around the pelvis, shoulder, face or elsewhere. Muscular dystrophy can affect adults, but the more severe forms tend to occur in early childhood.

There is no specific treatment for any of the forms of muscular dystrophy. Physical therapy to prevent contractures (a condition when an individual with a muscular dystrophy grows and the muscles don't move with the bones and can easily be slowed down and/or make the individual's body straighter by daily physical therapy), orthoses (orthopedic appliances used for support) and corrective orthopedic surgery may be needed to improve the quality of life in some cases. The cardiac problems that occur with Emery-Dreifuss muscular dystrophy and myotonic muscular dystrophy may require a pacemaker. The myotonia (delayed relaxation of a muscle after a strong contraction) occurring in myotonic muscular dystrophy may be treated with medications such as quinine, phenytoin, or mexiletine but no actual long term treatment has been found.

MYO-029 is an experimental myostatin inhibiting drug developed by Wyeth Pharmaceuticals for the treatment of muscular dystrophy. Myostatin is a protein that inhibits the growth of muscle tissue, MYO-029 is a recombinant human antibody designed to bind and inhibit the activity of myostatin. A 2005/2006 trial was completed by Wyeth in Collegeville, PA. As of April 2007, the results of the study have not yet been made public, but it is one of the few known drugs in development for the treatment for muscular dystrophy.

Congenital muscular dystrophy includes several disorders with a range of symptoms. Muscle degeneration may be mild or severe. Problems may be restricted to skeletal muscle, or muscle degeneration may be pair with effects on the brain and other organ systems. A number of the forms of the congenital muscular dystrophies are caused by defects in proteins that are thought to have some relationship to the dystrophin-glycoprotein complex and to the connections between muscle cells and their surrounding cellular structure. Some forms of congenital muscular dystrophy show severe brain malformations, such as lissencephaly and hydrocephalus.[4]

Duchenne muscular dystrophy (DMD) is the most common childhood form of muscular dystrophy. DMD usually becomes clinically evident when a child begins walking. Patients typically require a wheelchair by age 10 to 12 and die in their late teens or early 20s. In the early 1990s, researchers identified the gene for the protein dystrophin which, when absent, causes DMD. The dystrophin gene is the largest known gene in humans. Since the gene is on the X-chromosome, this disorder affects primarily males. Females who are carriers have milder symptoms. Sporadic mutations in this gene occur frequently, accounting for a third of cases. The remaining two-thirds of cases are inherited in a recessive pattern.
age at onset: two to six years; symptoms include general muscle weakness and wasting; affects pelvis, upper arms, and upper legs; eventually involves all voluntary muscles; survival beyond 20 years is rare.[4]
Dystrophin is part of a complex structure involving several other protein components. The "dystrophin-glycoprotein complex" helps anchor the structural skeleton within the muscle cells, through the outer membrane of each cell, to the tissue framework that surrounds each cell. Due to defects in this assembly, contraction of the muscle leads to disruption of the outer membrane of the muscle cells and eventual weakening and wasting of the muscle.[4]

Age at onset, childhood to early teens. Symptoms include weakness and wasting of shoulder, upper arm, and shin muscles; joint deformities are common; progress is slow; sudden death may occur from cardiac problems.[12]

FSHD initially affects muscles of the face, shoulders, and upper arms with progressive weakness. Symptoms usually develop in the teenage years. Some affected individuals become severely disabled. The pattern of inheritance is autosomal dominant, but the underlying genetic defect is poorly understood. Most cases are associated with a deletion near the end of chromosome 4.[4]

LGMD's all show a similar distribution of muscle weakness, affecting both upper arms and legs. Many forms of LGMD have been identified, showing different patterns of inheritance (autosomal recessive vs. autosomal dominant). In an autosomal recessive pattern of inheritance, an individual receives two copies of the defective gene, one from each parent. The recessive LGMDs are more frequent than the dominant forms, and usually have childhood or teenage onset. The dominant LGMDs usually show adult onset. Some of the recessive forms have been associated with defects in proteins that make up the dystrophin-glycoprotein complex.[4]

Myotonic muscular dystrophy is the most common adult form of muscular dystrophy. It is marked by myotonia as well as muscle wasting and weakness. Myotonic dystrophy varies in severity and manifestations and affects many body systems in addition to skeletal muscles, including the heart, endocrine organs, eyes, and gastrointestinal tract. Myotonic dystrophy follows an autosomal dominant pattern of inheritance. Myotonic dystrophy results from the expansion of a short repeat in the DNA sequence (CTG in one gene or CCTG in another gene). In other words, the gene defect is an abnormally long repetition of a three- or four-letter "word" in the genome. While the exact mechanism of action is not known, this molecular change may interfere with the production of important muscle proteins.[4]

Oculopharyngeal MD's age at onset: 40 to 70 years; symptoms affect muscles of eyelids, face, and throat followed by pelvic and shoulder muscle weakness, has been attributed to a short repeat expansion in the genome which regulates the translation of some genes into functional proteins.[4]

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